The goal of this research is to use Raman spectroscopy techniques to study the sequence dependent conformations of tetraplex DNA and RNA molecules under various conditions, such as in crystals and solutions. Our initial effort focussed on characterizing the short I motif structures of d(C4) crystal which is known to consist solely of I-motif tetraplexes with all cytosines involved in C:C+ base pairs. Single crystals were examined with Raman microspectroscopy. We have also examined these tetraplexes in soultion state. the bes . This should provide an excellent case for the assignment of Raman bands. The behavior of tetraplexes and C-rich oligonucleotides is dependent on pH. Near the pKa for cytosine N3 (pH 4.3), we would expect a transition from "single-stranded" species to intercalated C:C+ tetraplexes. Initial results indicate that these transitions can be monitored spectroscopically in aqueous solution. Currently experiments are bing carried out on C-rich sequences including d(TAACCC), d(AACCC), and d(CCCT).